biostudies-literatureMaurya AKNational Institutes of HealthNIGMS NIH HHS5642-5649.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC8692433biostudies-literatureUnknown31(24)Primary cilia are microtubule (MT)-based organelles that mediate sensory functions in multiple cell types. Disruption of cilia structure or function leads to a diverse collection of diseases termed ciliopathies.^1-3 The highly conserved CCRK and RCK kinases (ICK/MOK/MAK) negatively regulate cilia length and structure in Chlamydomonas, C. elegans, and mammalian cells.^4-10 How the activity of this kinase cascade is tuned to precisely regulate cilia architecture is unclear. Mutations in the Domain of Unknown Function 3719 (DUF3719)-containing protein FAM149B1 have recently been shown to elongate cilia via unknown mechanisms and result in the ciliopathy Joubert syndrome.¹¹ Here we identify XBX-4, a DUF3719-containing protein related to human FAM149B1, as a regulCurrent biology : CBxbx-4, a homolog of the Joubert syndrome gene FAM149B1, acts via the CCRK and RCK kinase cascade to regulate cilia morphology.PMC8692433R35 GM122463Sengupta PMaurya AKfalsexbx-4, a homolog of the Joubert syndrome gene FAM149B1, acts via the CCRK and RCK kinase cascade to regulate cilia morphology.Primary cilia are microtubule (MT)-based organelles that mediate sensory functions in multiple cell types. Disruption of cilia structure or function leads to a diverse collection of diseases termed ciliopathies.^1-3 The highly conserved CCRK and RCK kinases (ICK/MOK/MAK) negatively regulate cilia length and structure in Chlamydomonas, C. elegans, and mammalian cells.^4-10 How the activity of this kinase cascade is tuned to precisely regulate cilia architecture is unclear. Mutations in the Domain of Unknown Function 3719 (DUF3719)-containing protein FAM149B1 have recently been shown to elongate cilia via unknown mechanisms and result in the ciliopathy Joubert syndrome.¹¹ Here we identify XBX-4, a DUF3719-containing protein related to human FAM149B1, as a regul2021-01-01T00:00:00Z2021 Dec2026-05-31T02:11:46.204Z2024-10-16T10:48:21.395ZS-EPMC86924333473167410.1016/j.cub.2021.10.027